The present invention relates to a method for creating tobacco addiction and in particular to a method in which symptoms of nicotine withdrawal syndrome are relieved, especially the craving for a tobacco product.
Jan. 1989 marks the 25th anniversary of the Surgeon General's report linking cigarette smoking to cancer, heart disease, respiratory disease and other conditions. Despite such information being available to the public, a report prepared by the Surgeon General to mark the anniversary concluded that cigarette smoking remains the single most important preventable cause of death in the United States.
Benowitz, N. Eng. J. Med. Vol. 319, No. 20, pp. 1318-1330 (Nov. 17, 1988) notes that many people who smoke cigarettes would like to quit but cannot because they are addicted to the psychoactive drug that is the dependence-producing constituent of tobacco, nicotine.
Benowitz notes that nicotine may also contribute to the diseases for which smoking is a risk factor, particularly heart disease. Nicotine is also present in other tobacco products that are smoked or chewed, which are also addictive and associated with heart and lung disease.
Once nicotine enters the bloodstream it has been shown to cross the blood brain barrier and bind to receptors in the brain, resulting in the release of the neurotransmitter serotonin in the central nervous system's neurohumoral pathways. While nicotine's effect on the neurotransmission of serotonin and the receptors of the presynaptic membrane are poorly understood, it is believed that abstinence from tobacco and nicotine results in the reuptake and accumulation of serotonin in these neurohumoral pathways, that when the release of which is not stimulated by nicotine, results in the symptoms of nicotine withdrawal.
According to Benowitz, in about 80% of tobacco users, the cessation of tobacco use results in the development of nicotine withdrawal syndrome, the symptoms of which include restlessness, irritability, anxiety, drowsiness, increasingly frequent wakings from sleep, impatience, confusion, impaired concentration, carbohydrate craving and weight gain, impaired reaction time and a craving for tobacco. While most symptoms peak within 24 to 48 hours after tobacco use is discontinued, and gradually diminish over a two week period, other symptoms, particularly the craving for tobacco persist for months and even years. This craving for tobacco is the overwhelming reason why so many individuals who try to quit smoking fail to succeed.
Pharmacologic therapies are known to help those addicted to nicotine. Receptor antagonists such as mecamylamine have been used that reduce the satisfaction obtained from tobacco use. This therapy has been unsatisfactory because it has a short term effect of increasing tobacco consumption to overcome the receptor antagonism as well as the number of undesirable side-effects.
Non-receptor antagonists have also been used, such as clonidine, that act upon the alpha.sub.2 adrenergic receptors of the central nervous system and reduce the intensity of the craving for tobacco and other tobacco withdrawal symptoms. According to Benowitz, in one recent study clonidine treatment for six weeks was found to be more effective than a placebo, but only for women.
Benowitz reports that the most effective pharmacological approach thus far has been nicotine substitution therapy, using nicotine gum, or other nicotine forms, to slowly wean individuals from their addiction to nicotine and craving for tobacco products containing same. The problem with nicotine substitution therapy is that it involves the administration of the psychoactive constituent of tobacco indicated as a contributor to the diseases for which smoking is a risk factor. Nicotine substitution, additionally, must be tapered leading to nicotine withdrawal and subsequent relapse to smoking on a frequent basis. A therapy that relieved nicotine withdrawal symptoms particularly the long term cravings for nicotine, without the hazards associated with the administration of nicotine, would be highly desirable.